Plasmapheresis is a process of separating plasma from whole blood. The plasma-depleted blood is comprised principally of cellular components, e.g., red blood cells, white blood cells and platelets. Plasma is comprised largely of water, but also contains proteins and various other noncellular compounds, both organic and inorganic.
Continuous plasmapheresis is the process of continuously separating plasma from whole blood.
Plasmapheresis is currently used to obtain plasma for various transfusion needs, e.g., preparation of fresh-frozen plasma, for subsequent fractionation to obtain specific proteins such as serum albumin, to produce cell culture media, and for disease therapies involving either the replacement of plasma or removal of specific disease-contributing factors from the plasma.
Plasmapheresis can be carried out by centrifugation or by filtration. Generally, in known filtration apparatus, whole blood is conducted in a laminar flow path across one surface, i.e., the blood side surface, of a microporous membrane. Useful microporous membranes have pores which substantially retain the cellular components of blood but allow plasma to pass through. Such pores are referred to herein as cell-retaining pores. Typically, cell-retaining pore diameters are 0.1 .mu.m to 1.0 .mu.m.
In such known apparatus, as the blood flows through the flow path, the cellular components tend to migrate towards the center or axis of the path. Ideally, plasma occupies the periphery of the path so that it is predominantly plasma that contacts the membrane. A pressure difference across the membrane causes some of the plasma to pass through the pores of the membrane while plasma-depleted blood continues to flow to the end of the path. Ideally, the filtrate is cell free; the plasma-depleted blood collected at the end of the flow path is concentrated, i.e., is depleted in plasma and therefore has an increased hematocrit (volume percent of red blood cells).
After blood has been conducted across the surface of a membrane at normal venous flow rates for some time, the transmembrane flow of plasma becomes impaired. This phenomenon is herein sometimes referred to as membrane fouling or simply as fouling. Known techniques for reducing fouling, i.e., increasing the length of time for which the process can be carried out without the occurrence of significant impairment of plasma flow, include varying the flow path size so as to optimize the wall shear rate along the length of the flow path as disclosed in U.S. Pat. 4,212,742, and recycling a portion of the plasma-depleted blood to increase the velocity of blood in the flow path; the latter technique may result in less plasma-depletion.
Various filtration devices for plasmapheresis are disclosed in the literature. U.S. Pat. No. 3,705,100 discloses a center-fed circular membrane having a spiral flow path. U.S. Pat. No. 4,212,742 discloses a device having divergent flow channels. German Pat. No. 2,925,143 discloses a filtration apparatus having parallel blood flow paths on one side of a membrane and parallel plasma flow paths, which are perpendicular to the blood flow paths, on the opposite surface of the membrane U.K. Patent Application No. 2,037,6l4 discloses a rectilinear double-membrane envelope in which the membranes are sealed together at the ends of the blood flow path. U.K. Patent Specification No. 1,555,389 discloses a circular, center-fed, double-membrane envelope in which the membranes are sealed around their peripheries. German Pat. No. 2,653,875 discloses a circular, center-fed double-membrane device in which blood flows through slot-shaped filter chambers
It is an object of this invention to provide a process and apparatus for plasmapheresis by filtration. It is a further object to provide such a process and apparatus whereby highly concentrated, plasma-depleted blood can be continuously collected without significant hemolysis and with reduced membrane fouling.